Abstract

RATIONALE Adherence to evidence-based cardiovascular (CV) medications after an acute myocardial infarction (AMI) is low after the first six months. The use of fixed-dose combinations (FDC) have been shown to improve treatment adherence and risk factor control in previous trials with various CV risk profiles. However, no randomized clinical trial has analyzed the impact of a FDC strategy on adherence in post-MI patients including factors affecting patients’ adherence to treatment.METHODSFOCUS (Fixed Dose Combination Drug for Secondary Cardiovascular Prevention) consisted of cross-sectional study (Phase 1) aimed to elucidate factors that interfere with appropriate adherence to CV medications for secondary prevention after an AMI. A 5-country cohort (Argentina, Brazil, Italy, Paraguay, and Spain) of 2118 patients was analyzed. In addition, 695 patients from phase 1 were randomized into a controlled clinical trial (Phase 2) to test the effect of a FDC polypill containing aspirin 100 mg, simvastatin 40mg and ramipril 2.5, 5 or 10 mg on adherence, blood pressure and low density lipoprotein cholesterol (LDL-C), as well as safety and tolerability over a period of 9 months of follow-up. Patients were randomized to either the polypill or the three drugs separately. Primary end-point was adherence to treatment measured the self-report Morisky-Green questionnaire (MAQ) and pill count.RESULTSIn phase 1, overall CV medication adherence defined as a MAQ score ≥16 was 89% and as MAQ score 20 was 45.5%. In a multivariable regression model, the risk of being non-adherent (MAQ<20) was associated with younger age, depression rating scale, being on a complex medication treatment, poorer health insurance coverage, a lower level of social support, with consistent findings across countries. In Phase 2, the FDC group showed improved adherence compared to the group receiving separate medications after 9 months follow up: 63% vs 52% (p=0,006) when using MAQ plus pill count to assess adherence. Adherence was also higher in FDC group when measured by MAQ alone (68% vs. 59%, p=0.049) or pill count alone (92% vs. 82%, p=0.002). No treatment difference was found at follow-up in mean SBP (129.6 vs 128.6 mmHg) nor in mean LDL-C levels (89.9 vs 91.7 mg/dL) nor in serious adverse events (23 [6.6%] vs. 21 [6%]) or death (1, 0.2% in each group).CONCLUSIONS AND RELEVANCEIn secondary prevention following an AMI, younger age, being depressed and following a complex drug treatment are associated with a lower medication adherence, while adherence is increased in patients with higher levels of insurance coverage and social support. Compared with the three drugs given separately, the use of a polypill strategy increased self-reported and direct measured medication adherence for secondary prevention following an AMI.